Non-phenolic diarylheptanoid from curcuma comosa protects against thioacetamide-induced acute hepatotoxicity in mice

Abstract

© 2020 Faculty of Pharmacy. Curcuma comosa Roxb. (C. comosa, Zingiberaceae) is a medicinal herb containing diarylheptanoids with anti-oxidative and anti-inflammatory activities. The crude extract and its phenolic diarylheptanoid were shown to have hepatoprotection in vitro. The present study investigated the active principles and their underlying mechanisms that provided protection against thioacetamide (TA)-induced hepatotoxicity in vivo. Hepatic injury was induced in adult male mice by a single injection of TA (50 mg/kg BW, i.p.). C. comosa ethanol extract (5-500 mg/kg BW, p.o.), isolated diarylheptanoids: (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol, (D-049) or (3S)-1-(3,4-dihydroxy-phenyl)-7-phenyl-(6E)-6-hepten-3-ol, (D-092), (1-25 mg/kg BW, i.p.), was given prior to receiving TA. Changes in plasma activity of alanine transaminase (ALT), hepatic glutathione (GSH) content, the activities of superoxide dismutase (SOD) and catalase (CAT), and the expression levels of tumor necrosis factor (TNF-α) and cytochrome P450 2E1 (CYP 2E1) were determined at 24 h after TA-treatment. C. comosa extract suppressed the elevation of plasma ALT level in the TA-induced acute hepatotoxicity with increases in hepatic SOD and CAT activities. The protective effect was observed at 1 and 6 h prior to receiving TA and the effective dose was at 25 mg/kg BW. For pretreatment with diarylheptanoids, only non-phenolic diarylheptanoid, D-049 (5-25 mg/kg BW), provided the protection, but not phenolic diarylheptanoid, D-092. Moreover, D-049 suppressed the expression of pro-inflammatory cytokine TNF-α and CYP 2E1. These findings suggest that D-049 is an active principle in C. comosa that contributes hepatoprotection against TA-induced oxidative damage. It may mediate through its increased intracellular antioxidant enzymatic detoxification, which subsequently decrease the formation of bioactive metabolites of TA.